PMID- 10563711
OWN - NLM
STAT- MEDLINE
DCOM- 19991123
LR  - 20190718
IS  - 0269-9370 (Print)
IS  - 0269-9370 (Linking)
VI  - 13
IP  - 16
DP  - 1999 Nov 12
TI  - Subcutaneous adipocyte apoptosis in HIV-1 protease inhibitor-associated 
      lipodystrophy.
PG  - 2261-7
AB  - BACKGROUND: Inhibitors of HIV-1 protease produce a rapid decrease in plasma HIV-1 
      RNA, with concomitant immune reconstitution. However, severe metabolic side 
      effects together with a previously unseen form of lipodystrophy have been 
      associated with long-term use of protease-inhibitor therapy. The pathogenic 
      mechanisms underlying HIV-1 protease inhibitor-associated lipodystrophy are still 
      largely unknown. METHODS: Fourteen HIV-infected patients with HIV-1 protease 
      inhibitor-associated lipodystrophy had a biopsy of subcutaneous fat performed in 
      the antero-lateral aspect of the right leg. The samples were submitted for 
      standard pathologic study together with a careful search for adipocyte apoptosis. 
      Apoptosis was assessed by the terminal deoxynucleotidyl transferase 
      dUTP-digoxigenin nick end labelling (TUNEL) method, using the ApopTag kit (Oncor, 
      Gaithersburg, Maryland, USA). The procedure was performed between three and five 
      times for each sample. Appropriate positive and negative controls were used. 
      Controls which were subcutaneous fat biopsies from patients with untreated 
      melanoma were also examined for the presence of apoptosis. RESULTS: Fourteen 
      HIV-infected patients with a mean exposure to HIV-1 protease inhibitors of 12.6 
      +/- 3.7 months (range: 6-21 months), developed the characteristic features of 
      HIV-1 protease inhibitor-associated lipodystrophy. All but one patient had an 
      abnormal waist:hip ratio, and they all exhibited an abnormal serum lipid profile. 
      Pathologically, subcutaneous fat atrophy was a constant feature, along with focal 
      lipogranuloma formation and vascular proliferation. One of the eleven assessable 
      biopsy samples was negative for the presence of apoptosis, six showed focally 
      positive apoptotic cells, and the remaining four biopsies demonstrated moderate 
      positivity. Apoptotic changes were also detected in endothelial cells. Apoptotic 
      changes were more pronounced in patients with higher increases in CD4 and CD8 
      counts, and in those with a greater decay in plasma viral load. CONCLUSIONS: 
      Subcutaneous adipocyte apoptosis occurs in lipoatrophic areas of patients with 
      HIV-1 protease inhibitor-associated lipodystrophy.
FAU - Domingo, P
AU  - Domingo P
AD  - Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, 
      Universitat Autonoma de Barcelona, Spain. pere.domingo@cc.uab.es
FAU - Matias-Guiu, X
AU  - Matias-Guiu X
FAU - Pujol, R M
AU  - Pujol RM
FAU - Francia, E
AU  - Francia E
FAU - Lagarda, E
AU  - Lagarda E
FAU - Sambeat, M A
AU  - Sambeat MA
FAU - Vazquez, G
AU  - Vazquez G
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PL  - England
TA  - AIDS
JT  - AIDS (London, England)
JID - 8710219
RN  - 0 (Anti-HIV Agents)
RN  - 0 (HIV Protease Inhibitors)
SB  - IM
MH  - Adipocytes/*pathology
MH  - Adult
MH  - Anti-HIV Agents/adverse effects/therapeutic use
MH  - Female
MH  - HIV Infections/*drug therapy
MH  - HIV Protease Inhibitors/*adverse effects/therapeutic use
MH  - HIV-1/enzymology
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Lipodystrophy/chemically induced/*pathology
MH  - Male
MH  - Middle Aged
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
AID - 10.1097/00002030-199911120-00008 [doi]
PST - ppublish
SO  - AIDS. 1999 Nov 12;13(16):2261-7. doi: 10.1097/00002030-199911120-00008.